Although blood and plasma are screened for hepatitis C virus (HCV), some cases continue to occur after blood transfusion due to window period cases; in addition, the frequent spontaneous mutations of this virus make it difficult to develop a vaccine against the virus and also make it necessary to ensure that the existing assays can detect all mutants. The greatest degree of mutation occurs at the hypervariable region of the virus (HVR) coded in the E2 region. We had the unique opportunity to study the changes in the HVR of HCV over a 25- year period in a nurse who was infected with chronic HCV by a needlestick contaminated with the blood of a patient with HCV. Serum samples were available from both the nurse and the original source patient over a 25-year period. HCV RNA was extracted from these frozen sera and sequenced. Rapid sequence changes in the HVR were compared with each other (in different serum samples obtained over the 25-year period) and contrasted with the highly stable 5'-noncoding (5'-NC) region. The sera from the nurse have been completely tested and are being analyzed; the sera from the source patient will be studied in the next fiscal year. Nearly all studies of HCV variations published to date have focussed on the HVR, the 5'-NC, or the NS5 regions of the gene. None have examined the core region, despite increasing evidence that the core region of HCV may play a deciding role in the pathogenesis of the disease that HCV causes. Although HCV is primarily a cytoplasmic virus, truncated portions of the core protein have been shown capable of entering the nucleus of the hepatocyte, providing a possible mechanism of the virus' actions. A project is underway to evaluate gene sequences of the HCV core gene (gene encoding one of the important proteins in the licensed assays to detect anti-HCV) in 17 patients from Miyazaki, Japan, 10 patients from Kurume, Japan, and 5 Canadian patients. Analysis of these sequences, in comparison to those from control patients with lesser degrees of clinical infection, will provide important information about the virus.